This application requests funds to purchase an integrated Positron Emission and X-ray Computed Tomography (PET-CT) Imaging system for use in numerous funded research studies involving human subjects or large animals at Vanderbilt University. PET imaging is the primary molecular imaging method available for non-invasive, translational human studies. Because of its high sensitivity and the availability of a wide range of biologically relevant radiotracers, PET can be used (amongst others) to detect and diagnose cancer, to assess specific cellular and molecular characteristics of tumors, to quantify brain neurochemistry and metabolism, to study the distributions and effects of novel pharmaceuticals, and to report on multiple cellular and molecular imaging biomarkers in a variety of important clinical applications. In the brain PET is uniquely capable of assessing neurotransmitter levels, occupancies and transport in neuropsychiatric applications, and is a crucial tool in the evaluation of novel drugs and interventions. In cancer, PET is a primary modality for use as a biomarker of tumor phenotype, treatment response and for characterizing the effects of novel targeted treatments at a molecular level. The uses and applications of PET rely on the availability of suitable radionuclides that are labeled with positron-emitting atoms such as 19F and 11C. Vanderbilt has a well- established PET Center and cyclotron, along with extensive radiochemistry laboratories and personnel, but the only PET scanner reliably available for research studies is a microPET that cannot accommodate people or large animals. The requested instrument would meet the extensive demand for research PET studies of humans and large animals in a leading medical center. Moreover, as all modern PET scanners also incorporate CT for co-registration, the proposed instrument would also provide access for research CT studies as well. Although we possess dedicated CT scanners for small animals, we have no research CT capability for human subjects and imaging of large animals is not allowed by law on our clinical systems. The PET-CT scanner would provide new types of information that will complement and enhance the ongoing research of numerous NIH-funded projects, SPORES and Centers, and would be a unique resource for multiple investigators. The Radiochemistry Center at Vanderbilt is experienced in producing an array of compounds that will be used to study tumor metabolism, hypoxia and proliferation, the expression levels of specific cell receptors and proteins, and various neuroreceptors, transporters and modulators. Several of the CT applications are focused on the development of image-guided interventions. The system will be housed and managed in a dedicated Institute of Imaging Science that is experienced in providing and operating major core shared research resources for investigators, and will be supported by an expert staff and user group. A comprehensive plan for Administration and Financial Management of the resource has been developed.